Successful treatment of medical conditions and/or disease is not only dependent on novel active pharmaceutical ingredients (API), but it is also dependent on providing novel and effective pharmaceutical dosage forms to ensure delivery of the API to the intended target site within the human or animal being treated. In order to achieve effective API delivery at the intended site due consideration must be given to where the intended target is within the body, and to the physiological obstacles that may prevent effective delivery via various routes of administration.
Often the time taken for the API to reach its target site is also important. This is of particular importance in API's that provide pain relief or allergy relief.
Extensive research has been conducted in the field of biocompatible polymers which have been developed to provide effective pharmaceutical dosage forms. These polymers are then formulated into various solid dosage forms such as wafers, tablets and capsules depending on their physico-chemical and/or physico-mechanical properties.
Wafer technology is already used within the pharmaceutical industry as a species of pharmaceutical dosage form. Wafers are typically used when needing to deliver API through the mucosal membrane of the mouth cavity. Essentially, the wafer incorporates at least one active pharmaceutical ingredient (API) to be released in use. When formulating wafers, one needs to consider several variables, including, but not limited to the fact that: the API should be rapidly absorbed through the mucosal membranes in the mouth via transmucosal absorption; wafer technologies typically attempt to deliver API's that cannot be effectively delivered via conventional oral solid dosage (OSD) forms (for reasons including that the API has a low gastric bioavailability, and that normal OSD's may result in nausea of the patient making them unsuitable); a low dose of the API is typically required since the dosage form is not subjected to passage through the entire gastro-intestinal tract; and rapid action is often required, especially where pain and/or allergy relief is required.
Known wafer technology typically relies on the formulation of the active pharmaceutical ingredient (API) within a water soluble polymeric/excipient blend to dissolve rapidly in the mouth, thereby releasing the API for absorption and transport to its desired target. To be effective, the formulation requires that the following performance aspects are met: the polymers and/or excipients used to manufacture the wafer must be soluble at physiological temperature (about 37 qC) without the aid of heating or stirring; the API taste must be masked by the excipients; the wafer should not be excessively hygroscopic and must have an acceptable shelf life; the total wafer size should not exceed a diameter of about 2 cm and the mass should be less than about 800 mg for ease of use for the patient; and the wafers should dissolve completely and leave no residue after disintegration.
The manufacture of rapidly dissolving dosage forms, particularly wafer type dosage forms, for the rapid release of active pharmaceutical ingredient remains a difficult task. The lyophilized polymeric matrices of the dosage forms are not robust and present difficulty in handling with a risk of breaking when taking them out from the packaging (typically blister packs). Therefore, a specialized peel-off packaging is required for the same which further increases that final cost of the product. The complete solubility of the matrix components is very important as a gritty feel would compromise patient compliance. The disintegration, dispersion, and dissolution of the matrix should be very fast in order to provide enhanced permeability and taste-masking.
Existing products on the market include the Zydis® technology, which has been used for a number of commercial products including Claritin® Reditab®, Dimetapp® Quick Dissolve, Feldene® Melt, Maxalt-MLT®, Pepcid® RPD, Zofran® ODT®, and Zyprexa®. The existing products are known to use active pharmaceutical ingredients (APIs) including for examples: oxazepam, lorazepam, loperamide, and enalapril.
There is a need for novel and improved pharmaceutical dosage forms in order to improve effective delivery of APIs.